无源医疗器械CE技术文档和CE设计档案材料指南(中英文 也是极好的)

无源医疗器械技术文件和设计文档指南

Whereas the term “Technical File“ is used for Medical Devices of class I, class IIa and class IIb, the term “Design Dossier“ is used for the class III products.

标题中的“技术文件”适用于I类，IIa类,IIb类医疗器械，“设计文档”适用于III类医疗器械。

Technical Files are retained in the premises of the manufacturer or the Authorized Representative for potential review of Competent Authorities and Notified Body.

Part B of the Technical File may be available at the manufacturer only.

技术文件是保留在制造商或授权代表单位的主管部门和认证机构。部分技术文件B部分只保留在制造商处。

Whereas Design Dossiers have to be submitted to the Notified Body for review prior to CE-Marking of the product (use form Application for CE Conformity Assessment (Product)MED_F_03.03). We will assign a project manager who will entrust one or more further experts with the review of particular modules. All experts are at your disposal directly or indirectly through the project manager. After successful review, the Notified Body issues a design examination certificate according to Annex II.4 of the Council Directive certifying compliance with the relevant provisions of Annex I of the MDD.

设计档案材料已被提交到公告机构用于需要CE认证前的产品审查（用CE合格评定（产品）MED_F_03.03规定的格式）。我们将委派一个项目经理，他将委托一个或多个资深专家审查特定的模块。所有专家会直接或通过项目经理间接与你接触，在成功的审查后，公告机构会按照MDD法规附件I和附件II.4相关规定签发检验证书。

Article 5 of the Council Directive describes consideration of the European harmonized standards by the manufacturer in order to demonstrate compliance with the Essential Requirements.This aspect is even more important as International Standard Organizations have adopted European Norms (and vice versa) and demonstrating compliance with these standards could be very helpful in international mutual recognition of the CE-Marking process.

理事会指令5描述了制造商要遵守的欧洲统一标准，以证明附合基本要求，这方面更重要的是为国际标准组织已经通过了欧洲规范（反之亦然），并且遵守这些标准可能非常有助于国际的相互承认在CE认证过程中。

It is not necessary to include all documents in the Design Dossier which have already been subject to an ISO / EN / MDD Audit by the Notified Body. Examples of documents not necessary to be included are Quality Manuals and related lower level documents.

设计档案材料不必一定包括那些已经提交给ISO / EN / MDD审查公告机构的所有的文档，例如文档不必包括质量手册和一些相关更下层文档。

If the manufacturer of a class III device provides detailed information according to the checklist described below, the requirements of the Directive are appropriately addressed.

如果一个类III器件制造商提供详细的资料按下述清单，该指令的要求得到适当处理This is even more important in case a Competent Authority or another Notified Body

wishes to review the documentation.

这样很重要如果主管部门或其他认证机构要审查文件

Generally, the information should be provided as conclusions, summaries, reports, tables or flow charts (with reference to the full documentation in the Essential Requirement checklist).

一般的，提供的信息应包括结论，摘要，报告，表或流程图（参照完整文档在基本要求检查表中）

Special care should be taken to ensure that any information is consistent throughout the Design Dossier (e.g. description and variants of the device in different documents; adverse events as stated in the IFU and hazards in normal condition as well as in fault condition in the Risk Management).

特别应注意确保任何信息在整个卷中是一致的（例如：在不同的文档中器械的规格描述；说明书中不良事件的声明和在正常情况下的危害，以及在故障情况下的风险管理）

A complete pagination of the Design Dossier or another type of control mechanism is necessary, e.g. revision control of each section. Two copies of the documentation and an electronic version, if possible are required to achieve an appropriate review time. 设计档案材料必须有完整的页码控制或者另外形式的控制机制，例如，每个章节的版本控制。两份拷贝和一个电子版本，如果可能还需要一个审查时间。

In general, design changes described in the MDD (93/42/EEC), Annex II.4.4 shall be reported to the Notified Body (use form Change Notification MED_F_09.04) in order to ensure conformity with the requirements defined in the Annex II.4.4 and in order to ensure that the Design Dossiers retained at the Notified Body?s archive are complete and up-to-date.

一般来说，设计更改在MDD (93/42/EEC), 附肵II.4.4有说明，应向公告机构报告确保更改合适（按MED_F_09.04更改通知书格式）。

Furthermore at least one sample of the device should be provided.

此外，至少应提供一个设备样品

For all data SI units of measurement shall be used.

对于所有SI单位的测量数据应得到使用。

Important hint: Design Dossiers that accurately conform to the below guidance can be reviewed more efficiently!

重要提示：设计档案材料准确地符合以下指导可以更有效地进行审查

In this regard it is recommended to compile a Design Dossier or Technical File as follows

在这方面，建议编制设计档案材料或技术文件如下

(也可看NB-MED/2.5.1 和GHTF 文档SG1 (PD)/N011R20: STED):

PART A: Technical File A部分技术文件

1. Table of Content目录

2. Introduction介绍

3. Design Dossier/Technical File Summary Information设计档案材料/技术文件摘要信息

PART B: Annexes B部分附件

1. Essential Requirements Checklist基本要求检查表

2. Risk Analysis风险分析

3. Drawings, Design -, Product - Specifications图纸，设计- 产品- 规格

4. Chemical, Physical and Biological Tests化学，物理和生物测试

4.1 In Vitro Testing - Preclinical Studies体外试验- 临床前研究

4.2 In Vivo Testing - Preclinical Studies体内试验- 临床前研究

4.3 Biocompatibility Tests生物相容性测试

4.4 Bio-stability Tests生物稳定性试验

4.5 Microbiological Safety, Animal Origin Tissue微生物安全，动物保护组织

4.6 Drug / medical device combination药物/医疗设备组合

4.7 Blood Derivates, Human Tissue / medical device combination血液衍生物，人体组织/医疗设备组合

4.8 Coated Medical Devices涂层医疗器械

5. Clinical Data临床资料

6. Labels and Instructions for Use标签和使用说明

7. Manufacturing制造

8. Package Qualification and Shelf life包装和保质期

9. Sterilization灭菌

10. Conclusion结论

11. Declaration of Conformity (Draft)符合性声明（草稿）

PART A: Technical File A部分技术文件

1. Table of Content 目录

Content of both Parts A and B目录包括A部分和B部分

2. Introduction 介绍

? Revision history of Design Dossier: change notifications, revision numbers and approvals of all documents including all amendments.

设计文档案修订历史：更改通知，版本号和批准的所有文件，包括所有的修订

? Regulatory Information法规信息

o Name, postal address, Notified Body, certifications (valid copies attached!) of:

以下机构的名称，通讯地址，公告机构，证书（有效的复的复印件）

? the manufacturer (incl. contact person)制造商（包括联系人）

? OEM, critical suppliers, subcontractors (e.g. contract sterilizer) OEM，关键供应商，外协商（例如：合同灭菌商）

? European Representative (if applicable)欧盟代表（如果适用）

o Product and accessory classification, rule according to MDD, Annex IX and according to ISO 10993-1 Table 1 and 2

产品及配件分类：按照MDD规定的附录9和ISO10993-1表1和表2

o Conformity Assessment Route合格评定路径Annex II.3+II.4

o UMDNS-/GMDS-code UMDNS-/GMDS 编号

o Product History: approvals (e.g. FDA 510(k) or PMA clearance), market release, status of any pending request for market clearance; items sold 上市销售历史，证书，时间，数量

? Brief description of the product产品简要描述

o Intended use, model names, configurations, variants产品预期用途，型号规格名称，配置和规格表

o Accessories for the product, integral parts of package产品的附件,同一包装的部件o Applied standards (list or table including the full title, identifying numbers, date, and the organization that created the standard)适用标准（全名的列标，包括编号，日期和该标准的编制机构）特别协调标准

Note: Please make sure to use current standards only or provide a gap analysis

and rationale注：请务必使用唯一最新标准或提供差距分析和理由

o Rationale if applicable standards or parts thereof have not been considered 如为何没有采用当前标准或部分标准的理由

3. Design Dossier / Technical File Summary Information (reference to supporting documents filed in Part B)

设计档案材料/技术文件摘要信息（参照B部分支持文档）

? Comprehensive description of the system and each functional component of the device and the related accessories including utilized material or ingredient (animal/human origin, drug device combination?), packaging, method of sterilization, shelf life, combination with active medical devices. The description should be supported by diagrams, photographs or drawings, as appropriate.

综合描述：整个系统的（包括包装），产品的每个功能部件和相关的附件包括关键材料或组成部分（动物/人类,药物组合装置）,包装,灭菌方法,有效期,配合使用的有源医疗器械,描述应有适用的简图,照片或工程图.

? Basic scientific concepts that form the fundamentals for the device including medical,

biological, chemical, and physical background information

产品依据的基本的科学概念,包括材料,生物,化学和物理背景资料.

? In case of a Change Notification: description of all changes in comparison with the previous design or manufacturing process (e.g. tabular format)

更改通知:所有的变化描述与先前的设计或制造过程中的比较(例如:列表的格式)

? Summary of the essential data and results as detailed in Part B

B部分中关键数据和结果摘要

? Information as provided in the Instructions / Directions for Use (detailed in section B): Intended Use, Indication, Contraindications, Warnings, Adverse events, Operation and use of accessories

使用说明提供的信息:使用指导(详细见B部分),用途,标志,禁忌,警告,不良反应,操作和使

用的配件

? Planned changes计划中的改变（规格型号）

? Summary description of manufacturing process简要介绍制造过程

? Any other important safety/performance related information.任何其他重要的安全特性:性能相关的信息

This structure enables efficient project planning and management. Part A can be used for a pre-review in order to instantly notify the manufacturer of open issues or in case particular aspects are not covered in the Design Dossier.

这种结构应该能够有效的项目规划和管理。A部分可用于预先审查，以便即时通知制造商显尔易见的问题或某些具体方面没有包括在设计开发资料中的问题

PART B: Annexes B部分附件

1. Essential Requirements Checklist基本要求检查表

See also Attachment I: European Norms and Standards and other Documents supporting Technical Files and Design Dossiers.

另见附件I:欧洲的规范和标准及配套技术文件和其他设计档案材料

2. Risk Analysis风险分析

The document (Risk Management File) which describes the result of the risk management (including risk analysis, evaluation, mitigation and overall residual risk evaluation and production/post production information see ISO 14971 fig. B1 for an overview) process should contain at least the following information:

风险管理文档描述了风险管理的结果(包括风险分析,风险评估,风险降低和剩余风险评价以及按照ISO 14971 fig. B1进行的生产/生产后信息评价),风险分析程序到少包括下面和信息;

General information简要信息

o Summary概要

o Purpose of the document including project phase(s) / life cycle phase(s) for which the risk analysis was performed and reviewed Scope (e.g. design/product, manufacturing process, user/operation); product identification and description; intended use, shelf life.

文件的目的包括项目阶段（第）/风险分析进行的生命周期阶段（s）和审查范围(例:设计／生产制造程序，使用者／操作)；产品标识和说明，用途，有效期。

o Reference to: Risk Management SOP and Plan, Risk Management Policy, standards (EN ISO 14971, ISO 22442 part 1 -3 and MEDDEV 2.5-8 strongly recommended), specification documents, design documents, procedures, protocols, reports, manufacturing and production process information

参考：风险管理标准操作程序和计划，风险管理政策，标准（EN ISO 14971, ISO 22442 第1 -3 和MEDDEV 2.5-8强制执行），规范文件，设计文档，规程，协议，报告，制造和生产过程的信息

o Definition of terms, abbreviations and acronyms

术语定义，缩略语

o Participants of the risk analysis team (persons and organisations), their qualification,responsibility and authority.

风险分析团队（个人和组织），他们的证书，职责和权力。

o Note: the Risk Analysis shall include a medical knowledgeable and experienced

expert in the corresponding field of application.

注：风险分析应有一个具有医疗知识和相关领域应用经验的专家

o Note: The Risk Management Plan according to ISO 14971 -especially in relation to risk acceptance criteria- has to be defined by the top management under consideration of the estimated production volume to be sold per year and under consideration of regulatory requirements.

注：风险管理计划根据ISO 14971－尤其是有关风险接受准则－已被高层管理人员定义（考虑预计每年的产量和销售量以及监管规定）

o Identification of medical device characteristics that could impact on safety, e.g. according to ISO 14971.

识别可能影响安全的医疗设备的特征，例：参照ISO 14971

o If applicable consideration of data obtained from literature review, usability testing, market surveillance of similar devices, post market surveillance or post market clinical follow-up (also related to e.g. change notifications, predicate or otherwise comparable devices): complaint history, incidents per number of devices sold, analysis of underlying causes and final outcome, corrective and preventive action including proof of effectiveness

如果适用性审议的数据来自文献回顾，可用性测试，市场类似产品对比，产品售后信息和售后临床随访（其他相关的如：更改通知，其他方式类似装置）投诉历史，事故占销售设备的数量，分析事故原因及最终结果，纠正和预防措施，包括有效的证明。

o Revision history修订历史

Methodology评估方法

o Hazards / hazardous situations in normal condition: Hazard Analysis; patient/ user related (top-down approach), e.g. Fault Tree Analysis, table format

在正常状态下的危害/危害性情况;危害分析;病人/相关使用者(自上而下方法),例如:失效的树形分析,表格格式

? Clinical experience and clinical risks临床经验和临床风险

? Method for identification of applicable hazards; sources of information used

识别可适用性危害的方法;所用信息的来源

? Method for determination of the potential causes of hazards; sources of information used

判定危害的潜在原因的方法;所用信息的来源

? System used for categorization of severity levels (e.g. examples); description

of consequences to patients, users and other persons

严重程度的分类系统(例如:举例);对病人,用户和其它人产生的后果描述

? System used for categorization of occurrence of each hazard cause (probability estimate, frequency expressed as e.g. …events per device and time?)

每种危害原因产生的分类系统(可能性估计,频率表述为”根据器械和次数的事件”)

? Method for combination of severity and occurrence to risk level (e.g. diagram, graph, formula)

风险水平的严重和发生的组合方法(例如:图表,图形,公式)

? Criteria for risk acceptance (e.g. acceptable, ALARP, unacceptable) under consideration of the risk management plan and accumulated risks

考虑到风险管理计划和累计风险情况下的风险可接受性标准(例如:可接受,可操作又合

理的最低情况,不可接受)

? Note: If residual risks remain in ALARP region a rational should be ready to substantiate that no further mitigation was possible according to risk control

option analysis.

注意:如果剩余风险是在”可操作又合理的最低情况”的范围内,应该根据风险控制选择分析合理地证实没有其它的缓解措施.

o Hazards / hazardous situations in fault condition: e.g. FMEA; device related (bottom-up approach)

在失效状况下的危害/危害性情况:例如:潜在失效模式及后果分析;相关器械(自下而上方法)

? Method for identification of applicable failure modes; sources of information Used

适用的失效模式识别方法;所用信息来源

? Method for determination of the potential causes of failure modes; sources of information used

失效模式的潜在原因的判定方法;所用信息来源

? System used for categorization of severity levels; description of consequences

to patients, users and other persons

严重程度分类系统;对病人,用户和其它人所产生的后果描述

? System used for categorization of occurrence of each failure mode (probability estimate, frequency expressed as e.g. …events per device and time?)

每种失效模式发生的分类系统(可能性估计,频率表述为”根据器械和次数的事件”)

? System used for categorization of detectability of each failure mode (criteria

for detectability, frequency of in-process testing: 100%, sampling, or no testing

i.e. validated process)

每种失效模式的可检测性分类系统(可检测性标准,进程内测试频率:100%,抽样,或者无测试,也就是经验证的过程)

? Method for combination of severity, occurrence and detectability to risk level under consideration of the risk definition (see ISO 14971 2.16) (e.g. diagram, graph, formula)

在考虑风险定义(参见ISO 14971 2.16)(例如:图表,图形,公式)情况下, 风险程度的严重,发生和可检测的组合方法

? Criteria for risk acceptability (e.g. acceptable, ALARP, unacceptable) under consideration of the risk management plan and under consideration of accumulated risks

在考虑风险管理计划和累计风险情况下,风险可接受性的标准(例如:可接受, 可操作又合理的最低情况,不可接受)

? Note: If residual risks remain in ALARP region a rational should be ready to substantiate that no further mitigation was possible according to risk control

option analysis.

注意:如果剩余风险是在”可操作又合理的最低情况”的范围内,应该根据风险控制选择分析合理地证实没有其它的缓解措施.

Result (signed and dated documents): Risk Management Report结果(文件上有签字

和日期):风险管理报告

o Hazards / hazardous situations in normal condition正常状态下的危害/危害性状况: list of applicable hazards列出适用危害;

for each hazard (table format in hierarchical structure, if applicable)

对于每一种危害(层级结构的表格形式,如果适用的话)

? List of potential worst case effects (description of consequences to patients, users and other persons列出潜在的最坏情况的影响(对病人,使用者和其他人所产生的后果描述)

? List of potential causes of hazards as appropriate适当列出危害的可能原因

? Estimation of risk before mitigation (severity, occurrence, risk) including decision on acceptability缓解措施前的风险评估(严重,发生,危险),包括可接受性的判定

? Definition of risk reduction measures including reference to

methods (e.g. design, testing, manufacturing) and results of verification (implementation

and effectiveness)

风险降低措施的定义,包括方法(例如:设计,测试,制造),确认结果(实施和有效性)

? Estimation of risk after mitigation (severity, occurrence, risk) including decision

on acceptability under consideration of the risk management plan and under consideration of accumulated risks

在考虑风险管理计划和累计风险情况下, 缓解措施后的风险评估((严重,发生,危险), 包括可接受性的判定

? Risk / benefit weighting under consideration of the state of the art

在考虑工艺状态情况下的风险/获益权衡

o Hazards / hazardous situations in fault condition: list of applicable failure modes; for each failure mode (table format in hierarchical structure, if applicable):

在失效情况下的危害/危害性情况:列出适用的实失效模式;对于每种失效模式(层级结构的表格形式,如果适用的话):

? List of potential failure modes列出可能的失效模式

? List of potential worst case effects (description of consequences to patients, users and other) 列出潜在的最坏情况的影响对病人,使用者和其他人所产生的后果描述)

? List of potential causes of failures (as appropriate) 适当列出危害的可能原因

? Estimation of risk before mitigation (severity, occurrence, detectability, risk) including decision on acceptability

缓解措施前的风险评估(严重,发生,可接受性,危险),包括可接受性的判定

? Definition of risk reduction measures including reference to methods (e.g. design, testing, manufacturing) and results of verification (implementation and effectiveness) 风险降低措施的定义,包括方法(例如:设计,测试,制造)和验证结果(实施和有效性)

? Estimation of risk after mitigation (severity, occurrence, detectability, risk) including decision on acceptability

缓解措施之后的风险估计(严重,发生,可检测,危险),包括有关于可接受性的决定.

? Risk / benefit weighting under consideration of the state of the art在考虑工艺水平情况下的风险/获益权衡

o New hazards: Assessment of risks associated with new hazards in normal and

fault condition generated by risk mitigation measures. Corresponding risk reduction, if applicable

新危害:评估与在正常和失效状态下由风险缓解措施所产生的新危害有关联的危害. 相应的风险降低,如果适用的话.

? Final judgment, statement of对以下内容的最终判断,陈述:

o Completeness of risk evaluation风险分析的完整性

o Effectiveness of mitigation measures including a link to the verification documents 缓解措施的有效性,包括连接到验证文件

o Overall acceptability of residual risk剩余风险的整体可接受性

o Signed and dated by the team leader or responsible person团队领导或负责人签字并署上日期

3. Drawings, Design-, Product-Specifications图纸,设计和产品规格

? Comprehensive description of the product产品的综合描述

? Components and materials: complete chemical, biological and physical characterization部件和材料:完整的化学,生物和物理性特性描述

? Photographs, Blueprints照片,图纸

? Functional characteristics and technical performance specifications such as mechanical,

physical, electrical, biological, chemical, sterility, stability, packaging, transport, storage,combination with other medical devices, accuracy, sensitivity, specificity of measuring and diagnostic devices, reliability

功能性特征和技术性能指标,例如机械的,物理性的,电气的,生物的,化学的,无菌性,稳定性,包装,运输,存储,也其他医疗器械的组合,精确性,敏感性,测量和诊断器械的特异性,可靠性.

? Other important descriptive characteristics not detailed above以上未详述的其他重要的描述性特征

? Design Control (brief description) 设计控制(简单描述)

? QM (ISO 13485) Certificate of design facility 质量管理(ISO 13485)设计设施证书

? Final product release criteria including reference to verification test / validation

4. Chemical, Physical and Biological Tests化学,物理和生物测试

4.1 In Vitro Testing - Preclinical Studies体内测试-临床前研究

? In general testing must be conducted to predict the adequacy of device response to physiological and pathological stresses, undesirable conditions and forces, long-term use and all known and possible or foreseeable failure modes

一般来说,测试必须能预测器械应对生理和病理应力,不利因素和外力,长期使用和所有已知的和可能的或可预见的失效模式的妥善性

? Testing: e.g. visual, chemical, biological, physical/mechanical testing (i.e. tensile strength, durability, corrosion, fatigue, long term stability), efficacy / performance testing, simulated use

测试:例如视觉性,化学性的,生物性的,物理性的/机械性的测试(也就是拉力,持久性,腐蚀性,疲劳,长期稳定性),效能/性能测试,模拟使用.

? Finite Element Analysis if applicable如果适用的话,有限元分析

? Testing shall be performed on finished product (devices from the normal

manufacturing and after sterilization)

应对成品进行测试(成品指正常生产的并经过灭菌的)

? Otherwise, use of semi-finished devices, components, or raw materials must be characterized and justified

否则,使用半成品,部件或原材料必须是并合法化的.

? Drug Compatibility: Interaction between drug and device (e.g. adsorption)

药物相容性;药物和器械之间的交互作用(例如:吸附作用)

? Test protocols测试协议

o Purpose and objective of testing测试实物和目的

o Standard applicability matrix标准适用性模型

? List or table including the full title, identifying numbers, date, and the organization that created the standard包括全称,识别号,日期和编制标准的机构的清单或表格

? List of all sections列出所有的章节

? Justification if particular sections are not applicable如果特殊章节不适用的话,进行证实

? Reference to verification test / validation参考验证测试/确认

o Justification if applicable standards or parts thereof are not considered如果可适用标准或部分标准没被考虑的话,进行证实

? If other methods, such as internal standards are used, these methods shall be described in detail如果使用其他的方法,例如内部标准,这些方法要详细的进行描述.

o Accelerated and real time ageing and simulated distribution (package testing) prior to testing. Otherwise a justification is required

测试前的加速和实时老化以及模拟分配(包装测试).另外需要证实

o Conditions of accelerated ageing加速老化的条件

o For each test对于每个测试:

? Parameters to be measured and test description including reference to test procedure if applicable测量参数和测试描述,如适用的话,包括测试程序

? Measuring and testing equipment测量和测试设备

? Calibration arrangements校准安排

? Acceptance criteria验收准则

? Number of test samples including sample size rationale被测样品数量,包括样品尺寸基本原理

? Test reports测试报告

o Deviations and amendments to the protocols and justification偏差,协议和证实的修正

o Reference to raw data including date, laboratory, location, engineer, testing equipment (device number and calibration date)参考原始数据,包括日期,实验室,位置,工程师, 测试设备(设备号和效准日期)

o Statistical analysis统计分析

o Interpretation of data and conclusion(s)数据和结论阐述

o Approval signature(s)批准签字

4.2 In Vivo Testing - Preclinical Studies体外测试-临床前研究

Pre-clinical animal studies used to support the probability of effectiveness in humans

用于支持对人体的有效性的概率的临床前动物研究

? Good laboratory practice良好实验室研究规范

? Objectives, methodology, rationale for selecting the particular animal model including transferability to humans and limitations

用于选择特殊的动物模型包括对人类的转移性和局限性的目的,方法和基本原理

? Results, analysis (also statistical) of the functional effectiveness and the device's interactions with animal fluids and tissues

功能性效果的结果和分析,器械与动物流体和组织之间的交互作用的结果和分析(也是统计性的)

? Pharmacological / pharmacokinetical / toxicological studies i.e. purity, toxicity, ADME (adsorption, distribution, metabolism, elimination studies, LD50)

药理学/药动学/毒理学研究,也就是纯度,毒性,ADME

(即吸收、分布、代谢、排泄研究, LD50)

? Manufacturer's conclusions生产商的结论

4.3 Biocompatibility Tests生物相容性测试

The documentation in support of biocompatibility shall comprise the following:

? Biocompatibility testing plan生物相容性测试计划

o Purpose of the document, all applied standards文件的目的,所有适用的标准

o Scope, Description of the medical device适用范围,医疗器械的描述

? Intended use预期用途

? List of components/materials having direct or indirect body contact列出有直接或间接的人体接触的部件/材料

- Properties and characteristics of the finished product成品的性能和特性

- All materials used in the manufacture, including auxiliary materials, additives, process contaminants and residues, leachables, degradation products,

other components that do interact with the final product, etc., or refer to the applicable section of the Design Dossier

在生产中使用的所有的材料,包括辅助材料,添加剂,过程污染和残留物,滤除物,降解产物,其它与成品有交互作用的部件等等,或者参见设计档案材料的适用章节.

- Where appropriate define total surface area contacting the body or body

Fluids在适用的地方定义出与人体或人体流体有接触的整个表面区域

? Categorization of the medical device based on ISO 10993-1: Tables 1 and 2 according to:

根据以下内容以ISO 10993-1为基础的医疗器械分类::表1和表2:

- Nature of body contact人体接触的性质

- Contact duration接触持续时间

- The category defines which effects need to be considered at least分类定义至少哪些效果需要考虑

o Description of tested item(s) (finished device, part of device, raw material)

测试项目描述(成品,器械部件,原材料)

? Testing shall be performed on the final product or representative samples

taken from the final product or from materials processed in the same manner

as the final product (if applicable provide LOT/REF. No., etc.)

对从成品中或从以同样的方式进行处理的材料中抽出的成品或代表性样品惊醒测试(如

果适用,提供批号/参考编号等等)

? Rationale for the selection of the sample tested被测样品选择的基本原理

? Statement on the sterile state of the test sample. If the test sample was not sterilized, a rationale shall be given why sterilization has no influence on biocompatibility of the final device

关于被测样品无菌状态的陈述．如果测试样品不是无菌，应给出灭菌对成品的生物相容性不起作用的原因的基本原理．

? Assign appropriate tests to the biological effects. (Only such tests shall be performed which lead to evident results)指定适当的测试来测试生物性效应（只进行此类能产生明显结果的测试）

o Overview of tests to be performed in biological evaluation在生物学评价中所进行的测试的概观

? The selection and evaluation of any material or device intended for use in humans requires a structured programme of assessment (refer to ISO 10993-1

Annex B)

用于人体的任何材料或器械的选择和评估需要结构化的评估程序（参见ISO 10993-1中附录Ｂ）

o Justification for tests not performed未进行的测试的证实

? The quality and the extent of documentation as well as the assessment

in regard to the intended use determine whether or not biological

tests shall be performed with the final product and to what extent

关于预期用途的文件材料的质量和范围以及评估决定了是否对成品进行生物测试，以及进行到什么程度．

? Biological evaluation may include both a study of relevant experience and actual testing. Such an evaluation may result in the conclusion that no testing is

needed if the material has a documented history of use in a specified role that

is equivalent to that of the device under design

生物评估包括相关经验和实际测试的研究．这样的评估可能导致以下的结论：

如果材料有文件化的使用历史并在指定的作用方面等同于正在设计中的器械的使用历史，那么不需要测试．

? Each device should be examined on its own features. Data may be available

from suppliers or in the literature. In this case full transferability is to be demonstrated. Test systems, test sensitivity and concentrations used should be

taken into consideration

每种器械应根据其自身的特征进行检查．可从供应商或文献中获得数据．在此种情况下，将展示完全的可转移性．应考虑到用过的测试系统，测试敏感性和浓度．

? Waiving of tests shall be recorded弃权的测试应记录

? Biocompatibility test protocols (copies)生物相容性测试协议(复印件)

o Qualification of the test laboratory, i.e. accreditation测试实验室的资格验证，即认证o Testing should be conducted according to appropriate good laboratory practices followed by evaluation by competent informed persons

测试应按照适当的良好实验室规范进行，然后由权威的知情人士进行评估

o For qualitative data: acceptance criteria对于定性数据：验收准则

? Biocompatibility test reports (copies)生物相容性测试报告（复印件）

o For qualitative data/results: interpretation对于定性数据／结果：阐述

o Positive results – What to do?阳性反应－要做什么？

? Verification of results结果的确认

? Chemical characterization of leachables滤出物的化学特性

? Overall interpretation of the biological evaluation of the device器械的生物学评价的总体阐述

? Relevance of clinical use临床使用的相关性

Biocompatibility evaluation and summary report生物相容性评价和总结报告

o Compilation of tests performed in tabular form以表格的形式编制测试

Example例如:

Test测试

Protocol No.协议号

Project No./产品编号

Laboratory No.实验室编号

Report date 报告日期

Result结果

Conclusion结论

Cytotoxicity细胞毒性

Cytotoxicity test /细胞毒性测试

L 929-proliferation L 929-扩散

XY yyyy-mm-dd年－月－日

Growth analysis of cells cultured

with the test extract showed no

relevant growth inhibition of

L929 cells.

测试提取的培养细胞的生长分析未显示相关的L929细胞的生长抑制

Sensitization致敏性

Murine Local Lymph鼠性局部淋巴

Node Assay节点化验

YZ yyyy-mm-dd 年－月－日

The stimulation indices were

calculated to be less than 3.0.刺激指数要少于3.0.

o Further relevant information on the tests有关测试的更多相关信息

? Test sample (part tested) e.g. catheter shaft or tip, balloon, whole device

试样（部分测试）例如：管杆或导管尖端，气囊，整个器械

? Specification (polymer type, supplier, trade name, additives) e.g. PUR, Pellethane 2363-90A, 20% Ba2SO4

规格（聚合物类型，供应商，商品名，添加剂）例如：PUR, Pellethane

2363-90A, 20% Ba2SO4

? Status of test material (final product, sterile)

测试材料状态（成品，无菌）

? Type of body contact e.g. circulating blood

身体接触类型例如：血液循环

? Contact duration e.g. limited contact duration (< 24 h)

接触持续时间例如：限定的接触持续时间（＜24小时)

? Standard/norm e.g. EN ISO 10993-5: 1999

标准／规范例如：EN ISO 10993-5: 1999

? Extract preparation (medium, surface/mass to volume ratio, temperature, time)

提取准备（媒介，表面／质量体积比，温度，时间）

? Test lab qualification e.g. competence under DIN EN ISO/IEC 17025, certification acc. to GLP

测试实验室资格例如：DIN EN ISO/IEC 17025的资格认证，依据GLP的认证

? Action taken on positive results as described above

上述的对阳性反应采取的措施

o Conclusion结论

? Biological evaluation shall be part of the risk management process

生物学评价应是风险管理过程的一部分．

? A final statement of the manufacturer is necessary. The manufacturer might conclude that in his opinion, based on the submitted documentation, the product safety is ensured

生产商的最终陈述是必要的．生产商可能根据自己的意见，在所提交的文件材料基础上得出产品安全是受到保障的结论．

4.4 Bio-stability Tests生物稳定性测试

Influence of the biological matrix on the device, i.e.生物基质对器械的影响，即

? Surface Stress Cracking on Polymers高分子材料的表面应力断裂

? Corrosion of load-bearing metal screws承重金属螺丝的腐蚀性

? Coating Stability涂层稳定性

4.5 Microbiological Safety, Animal Origin tissue微生物安全, 动物源性的组织

? Geographical origin and boarding of animals: Species, Country, Herd, Feeding, Age 动物的地理来源：物种，国家，兽群，饲养，年龄

? Origin of material used/nature of starting tissue:

所用材料来源／组织的性质

? Specified risk material: organ, tissue, body fluid

指定危险物质：器官，组织，人体流体

? For TSE-relevant species: If available certificate of suitability of starting materials with respect to TSE issued by EDQM

对于与传染性海绵状脑病相关的物种：如果可获得与由EDQM签发的传染性海绵状脑病相关的原材料的适用性证书

? Veterinary controls动物控制

? Certificate demonstrating conformance with veterinary inspection criteria indicating that the raw material was fit for human consumption.

符合指示原材料适合人类消费的兽医学检测标准的证明证书

? Certificate documenting that the applied techniques for stunning and slaughtering were suitable to avoid cross contamination with specified risk material.(References: EN 12442-2/SSC guidelines/EC decisions.)

适用技术适合避免与规定的危险物质交叉污染的证书记录.（参见：EN 12442-2/SSC 向导/EC决定）

Risk analysis风险分析

? Risk analysis performed according to EN 14971 and EN 12442-1, including immunological,

toxicological, and liquid sterilization risks.

按照EN 14971和EN 12442-1所进行的风险分析,包括免疫学的,毒物学的,液体杀菌风险.

? Sum of Category Numbers (SCN) for TSE-relevant material only obtained according to

the following scheme

与传染性海绵状脑病相关的物质的类别编号总概仅根据以下的模式包含在内: Parameter Numbers of Risk categories风险类别的参数编号

1 2 3 4 CN

GBR IV

Incidence发生率

< 1:10000

GBR III

Incidence发生率

< 1:1 million百万

GBR II

Others其它

GBR I

No BSE, no

Risk风险

Geographical

Origin地理来源

Specified risk High risk Medium risk Low risk No risk规定的风险高风险中等风险低风险无风险

Material 物质

Inactivation钝化None无2-4 log 4-6 log > 6 log

Quantity/dose > 100 g 1-100 g 10 mg – 1 g < 10 mg

of raw material

原材料的数量/剂量> 100 g 1-100 g 10 mg – 1 g < 10 mg

Intracerebral大脑内的Other parenteral 其它肠胃外的

Mucous

membrane黏膜

Route of administration给药途径

External skin外部皮肤

Sum of Category Numbers (SCN)类别编号汇总:

Sum of Category Numbers (SCN) Significance and Consequences类别编号汇总意义和后果

20 Highest possible score, virtually no risk 20最高的可能得分, 最终无风险

> 12 Acceptable risk, that is lower than the risk of acquiring the sporadic form of human TSE (CJD) >12可接受风险,比获得人类TSE (CJD)

零星形式的风险要低

10-12 Risk is acceptable only if the disease is serious and

the benefit of the medical device is high and scientifically

well-established 10-12 只要疾病是严重的并且医疗器械的受益高且是科学确认的,那么风险是可接受的

6-9 Unacceptably high risk 6-9不可接受的高风险

west possibly score, unacceptably high risk 可能得分, 不可接受的高风险

Documentation of significant processing steps重要工序的文件材料

? A flowchart including the starting material and all intermediate and relevant process parameters

such as temperature, duration, and pH are required.

需要一个包含原材料和所有中介和相关的过程参数例如温度,持续时间和PH值的流程图? A detailed description of the manufacturing process including in-process controls

包括进程内控制的制造过程的详细描述

Procedure for reduction or inactivation of potentially existing infectious agents Documents on the systematic approach to gather information on new relevant zoonoses and infectious agents:

减少或钝化可能存在的感染性因素的程序

系统方法来收集关于新的人畜共患病和感染性因素的信息的文件:

? A validation study on virus inactivation / elimination including:

关于病毒钝化/消除的效度研究

? A current literature survey on relevant zoonoses

关于人畜共患病的现有文献调查

? Information on the production step with potential for inactivation

带潜在钝化的生产步骤信息

? The study protocol (including information on the test article, test organism, rational for the choice of relevant or model organism, indicator cell, virus titer, test method, controls, methods for calculating the results, scaling down, interference and cytotoxicity tests)

研究协议(包括关于测试物体,测试有机体,合理选择相关或生物模型,细胞的指标,病毒值,测试方法,控制,计算结果,按比例缩小,干扰和细胞毒性测试)

? The final test report最终测试报告

? The raw data原始数据

? Such a study is dispensable if the inactivation potential of the processing step under consideration is well established in the scientific literature.

如果潜在的处理步骤钝化在科学的文献中很好地建立,这样的研究并不是必要的. Slaughtering, transport, and handling屠宰,运输和处理

? Include a statement and respective certificates that requirements of Regulation 1774/2002/EC are met, that is: A certificate is required that the animals have received ante and post mortem inspection by a veterinarian and were deemed fit for human consumption.

包括满足规章1774/2002/EC要求的陈述和证书,即需要一个证书证明动物已经受到兽医宰后检验,认为适合人类消耗.

? Traceability, e.g. a lot-wise documentation of individual animals可追溯性,例如:个别动物的文件资料

? Measures adopted to avoid cross-contamination during slaughter, transport, and storage在屠杀,运输和储存中避免交叉污染所采取的措施

Combination with other medical devices和其它医疗器械的组合

Impact on the materials of animal origin对动物来源的材料的影响

Quantity of raw material per medical product每个医疗器械产品所用的原材料数量Raw material required for one daily dose: amount (mass in grams) used for production of the

single unit equivalent to one daily dose.

每日所要求的原材料: 用于单个单位生产的数量(质量公克),等同于每日1剂

Possible number of applications of medical device医疗器械应用的可能数量Number of daily doses每日剂量的数量

Route of application应用路径

Product coming into contact with the central nervous system region, central circulatory system, damaged/breached skin, mucosal membrane, undamaged skin, etc.

与中枢神经系统,中央循环系统, 受损或受破坏皮肤,黏膜,未受损皮肤等接触的产品.

A justification for the use of animal tissues or derivatives in the medical device, including a rationale for the acceptability of the overall (TSE) risk estimate, the evaluation of alternative materials, and the expected clinical benefit Clinical benefit

医疗器械中动物组织或衍生物使用的证实,包括总体风险估计的可接受性的基本原理,可选择材料的评估和临床受益.

? Justification for the use of material of animal origin 动物来源材料使用的证实

? Critical discussion of alternatives (e.g. synthetic,allogenic, autologous, or xenogenic material from non-TSE-relevant species)

可选用物的重要讨论(例如:来自于非传染性海绵状脑病相关物种的合成、同源,自体移植或异种物质)

? Unique characteristics of the product under consideration 考虑中的产品的独特特性Source establishments and/or third party suppliers for the animal material used 来源建立和/或所用的动物物质的第三方供应商

Documentation of the contractual agreements and the procedures in place with regard to the auditing of source establishments and/or third party suppliers for the animal material

关于来源建立和/或动物材料的第三方供应商的协约合同和在适当位置的程序的文件材料.

4.6 Drug / medical device combination药物/医疗器械组合

Considerations for the consultation procedure to the competent bodies of the member states or the EMEA regarding the assessment of usefulness and safety applied to a medicinal substance, which is of ancillary purpose, in a drug-device combination.

对成员国权威机构或欧洲药品评估局关于适用于药用物质的有用性和安全性评估的咨询程序方面的考虑, 这是药物器械组合的辅助性目的

? Guidance Documents and regulations向导文件和条例:

? MEDDEV 2. 1/3 rev 2

? Clinical Safety Data Management ICH E2 临床安全数据管理ICH E2

? Dose Response Information to Support Drug Registration ICH E4 支持药物注册的剂量反应信息

? Good Clinical Practice ICH E6药品优良临床试验规范

? Investigation of Drug Interactions (CPMP/EWP/560/95)

药品交互作用调查(CPMP/EWP/560/95)

? Bench Testing台架测试:

? Demonstration that the drug and device neither chemically nor physically interact adversely with each other

药物和器械之间相互的非化学性和非物理性不利作用演示

? Assessment how application of the drug and drug-carrier to the device may affect its fatigue and corrosion properties, coating integrity, durability, and any other relevant product-specific components.

药物和药物载体对器械的适用可能是怎样影响它的疲劳和腐蚀性能,涂层完整性,持续性和任何其他的相关特定的产品部件的评估.

? Pharmacodynamics (proof of concept)

药效学(概念验证)

? Non-clinical pharmacokinetic testing非临床药代动力学测试

? In vivo pharmacokinetic studies to quantify the duration of drug exposure.

量化药物暴露持续时间的药代动力学体外研究

? Drug concentrations should be measured at the local (tissue), regional (organ), and systemic levels in animals

应在动物体内局部(组织),区域(器官)和全身测量药物浓度.

? In the case of very small drug doses, time-release profiles usually suffice

to demonstrate safety for human trials在药物剂量非常小的情况下,文档资料通常能够演示人类实验的安全性

? Determination of the quantity of drug remaining on the device.

判定药物残留在器械上的药物量.

? Preclinical toxicity studies: Dosing studies to establish an efficacy margin between the sub-therapeutic dose and the therapeutic dose, and a safety margin between the therapeutic dose and the toxic dose. When polymer of carrier is present, additional controls to evaluate the carrier alone, without the drug, must be included.

临床前毒性研究:定量研究,建立一种效果之间的边缘亚治疗剂量和治疗剂量和治疗剂量的安全裕度之间,有毒的剂量。当聚合物的载体,额外的控制来评价,而药物载体,必须包括在内。

? Clinical testing of the active substance if not an approved medicinal product: Additional animal toxicity and human Phase I studies are to be expected if the drug component is not approved.

如果没有经批准的药品,临床测试活性物质:如果药物成分没被批准,就应该进行额外的动物毒性和人体第一阶段研究

? Clinical Data临床数据

? Clinical pharmacokinetic testing: Human toxicity Phase I studies are to be expected to determine the no observed adverse effect level (NOEL) if the drug component is not approved

临床的药代动力学测试:如果药物成分没被批准,就应该进行人类毒性第一阶段研究来判定

无明显的负作用水平

? Confirmatory clinical trials: When the medicinal substance of the combination is known to the competent authority and already registered in the setting of a DES and the applicant claims comparative medicinal substance release characteristics the use of clinical surrogate measures in the setting of a non-inferiority study against an approved device may be acceptable, provided that long-term safety concerns can be clearly ruled out for the claimed target population.

证实的临床实验: 当组合的药用物质当药用物质的组合是已知的,报请主管机关及已登记注册的设置一个DES和申请人要求比较药用物质释放特性的使用替代措施的临床研究的一个非低劣对认可的设备可以接受的,但长期的安全问题,可以清楚地排除的目标人群。

? For further requirements regarding Clinical Data see section 5.

更多关于临床诊断信息的要求参看第5部分

4.7 Blood Derivates, Human Tissue / medical device combination

血液衍生物,人类组织/医疗器械组合

? Human blood derivatives as specified in Annex I MDD, section 7.4 – only where the substance is liable to act upon the body with action ancillary to that of the device.

第7.4部分附录I MDD中规定的人类血液衍生物-物质是容易的身体和行为的配套设备

? Guidance Documents and regulations向导文件和规范:

? Note for Guidance on Plasma-Derived Medicinal Products CPMP/BWP/269/95

关于血浆源性医药产品的向导CPMP/BWP/269/95

? Note for Guidance on Assessing the risk for Virus Transmission - New Chapter 6 of the NfG on Plasma-derived medicinal products (CPMP/BWP/5180/03)

关于评估病毒传播风险的向导-关于血浆源性医药产品的NfG的新章节第6章

? Guideline on the Scientific Data Requirements for a Plasma Master File (PMF) (EMEA/CPMP/BWP/3794/03)

关于等离子体主文件的科学数据要求的向导(EMEA/CPMP/BWP/3794/03)

? Note for Guidance on virus validation studies: the design, contribution and interpretation of studies validating the inactivation and removal of viruses

(CPMP/BWP/268/95)

病毒效度研究的向导:确认病毒钝化和消除研究的设计,分发和阐述(CPMP/BWP/268/95)

? Relevant European Pharmacopoiea monographs相关的欧洲药典专著

? Guideline on the Investigation of Manufacturing Processes for Plasma-Derived Medicinal Products with regard to CJD Risk (CPMP/BWP/5136/03)

关于克雅氏病风险的血浆源性医药产品的生产过程调查向导

? CHMP Position Statement on CJD关于克雅氏病的人用药委员会声明

? The documentation should be provided in CTD format. A guideline to the contents is to be found in MEDDEV 2.1/3 part B:

? General information一般信息

? Description of the device (components, intended use)器械描述(成份,预期使用)

? Justification for the use of blood derivatives (intended purpose, suitability of the substance, critical evaluation of alternatives)

血液衍生物使用的证实(预期目的,物质的适用性,可选物的重要评估)

? Critical evaluation of the results of the risk analysis (potential risk in relation to the